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    CARS1 cysteinyl-tRNA synthetase 1 [ Homo sapiens (human) ]

    Gene ID: 833, updated on 10-Dec-2024

    Summary

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    Official Symbol
    CARS1provided by HGNC
    Official Full Name
    cysteinyl-tRNA synthetase 1provided by HGNC
    Primary source
    HGNC:HGNC:1493
    See related
    Ensembl:ENSG00000110619 MIM:123859; AllianceGenome:HGNC:1493
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CARS; MDBH; CYSRS; MCDDBH; MGC:11246
    Summary
    This gene encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. This gene is one of several located near the imprinted gene domain on chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2010]
    Expression
    Ubiquitous expression in thyroid (RPKM 12.8), brain (RPKM 10.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CARS1 in Genome Data Viewer
    Location:
    11p15.4
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (3000929..3057423, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (3090162..3146645, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (3022159..3078653, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2949927-2950535 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2950536-2951145 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2951146-2951754 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2954769-2955381 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:2961339-2961515 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2967017-2967632 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2967633-2968246 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2968247-2968862 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2968863-2969476 Neighboring gene pleckstrin homology like domain family A member 2 Neighboring gene NANOG hESC enhancer GRCh37_chr11:2982073-2982579 Neighboring gene nucleosome assembly protein 1 like 4 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:2986349-2986848 Neighboring gene MPRA-validated peak1165 silencer Neighboring gene small nucleolar RNA, H/ACA box 54 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:3012128-3012984 Neighboring gene Sharpr-MPRA regulatory region 13774 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:3035645-3036144 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:3051685-3052185 Neighboring gene CARS1 antisense RNA 1 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:3061281-3062480 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3063691-3064626 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3064627-3065562 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4307 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3078307-3078839 Neighboring gene uncharacterized LOC124902615 Neighboring gene RNA, U1 small nuclear 91, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:3083786-3084412 Neighboring gene MPRA-validated peak1169 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:3096337-3096837 Neighboring gene hESC enhancers GRCh37_chr11:3112372-3113180 and GRCh37_chr11:3113181-3113988 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3114797-3115604 Neighboring gene oxysterol binding protein like 5 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3075 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_21160 Neighboring gene Sharpr-MPRA regulatory region 6583 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3156337-3156944 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3156945-3157553 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:3157554-3158161 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3170165-3170940 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3170941-3171714 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3171715-3172488 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3174611-3175359 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:3178797-3179602 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:3180024-3180197 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:3184585-3185278

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Nucleotide and deduced amino acid sequence of human cysteinyl-tRNA synthetase. Cruzen ME, et al. DNA Seq, 1994. PMID 7987009
    2. Assignment of the cysteinyl-tRNA synthetase gene (CARS) to 11p15.5. Cruzen ME, et al. Genomics, 1993 Mar. PMID 8468064
    3. Cysteinyl-tRNA Synthetase Mutations Cause a Multi-System, Recessive Disease That Includes Microcephaly, Developmental Delay, and Brittle Hair and Nails. Kuo ME, et al. Am J Hum Genet, 2019 Mar 7. PMID 30824121, Free PMC Article
    4. Polymorphisms in CARS are associated with gastric cancer risk: a two-stage case-control study in the Chinese population. Tian T, et al. Gastric Cancer, 2017 Nov. PMID 28409418
    5. Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Hayano M, et al. Cell Death Differ, 2016 Feb. PMID 26184909, Free PMC Article

    See all (68) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CARS senses cysteine deprivation to activate AMPK for cell survival.
      Title: CARS senses cysteine deprivation to activate AMPK for cell survival.
    2. Endogenous TLR2 ligand embedded in the catalytic region of human cysteinyl-tRNA synthetase 1.
      Title: Endogenous TLR2 ligand embedded in the catalytic region of human cysteinyl-tRNA synthetase 1.
    3. Cysteinyl-tRNA Synthetase Mutations Cause a Multi-System, Recessive Disease That Includes Microcephaly, Developmental Delay, and Brittle Hair and Nails.
      Title: Cysteinyl-tRNA Synthetase Mutations Cause a Multi-System, Recessive Disease That Includes Microcephaly, Developmental Delay, and Brittle Hair and Nails.
    4. Four single nucleotide polymorphisms (SNPs) of CARS were significantly associated with gastric cancer risk in both the discovery stage and the validation stage
      Title: Polymorphisms in CARS are associated with gastric cancer risk: a two-stage case-control study in the Chinese population.
    5. The risk (G and C) and non-risk (C and T) allele frequencies of the SNPs at the rs1888747 and rs739401 loci of FRMD3 and CARS, respectively, did not differ significantly between the diabetics with (case) and without (control) nephropathy (P > 0.05).
      Title: Evaluation of associations between single nucleotide polymorphisms in the FRMD3 and CARS genes and diabetic nephropathy in a Kuwaiti population.
    6. Loss of CARS, the cysteinyl-tRNA synthetase, suppresses ferroptosis induced by erastin, which inhibits the cystine-glutamate antiporter known as system xc(-).
      Title: Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Replication study for the association between four Loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes.
    8. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: A three-stage genome-wide association study of general cognitive ability: hunting the small effects.
    9. CARS is a novel fusion partner of anaplastic lymphoma kinase in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor cases.
      Title: Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.
    10. Specificity of anticodon recognition by human CysRS is higher than that of its bacterial counterparts.
      Title: Kinetic quality control of anticodon recognition by a eukaryotic aminoacyl-tRNA synthetase.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Microcephaly, developmental delay, and brittle hair syndrome
    MedGen: C5394425 OMIM: 618891 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Joint influence of small-effect genetic variants on human longevity.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cysteine-tRNA ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cysteine-tRNA ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cysteine-tRNA ligase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables tRNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables tRNA binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables tRNA binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cysteinyl-tRNA aminoacylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cysteinyl-tRNA aminoacylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    cysteine--tRNA ligase, cytoplasmic
    Names
    cysteine tRNA ligase 1, cytoplasmic
    cysteine translase
    NP_001014437.1
    NP_001181926.1
    NP_001365065.1
    NP_001365066.1
    NP_001365067.1
    NP_001365068.1
    NP_001365069.1
    NP_001742.1
    NP_644802.1
    XP_047283628.1
    XP_047283629.1
    XP_047283630.1
    XP_054184847.1
    XP_054184848.1
    XP_054226099.1
    XP_054226100.1
    XP_054226101.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001014437.3 → NP_001014437.1  cysteine--tRNA ligase, cytoplasmic isoform c

      See identical proteins and their annotated locations for NP_001014437.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) includes an additional in-frame exon in the 5' coding region, and uses an alternate splice site that causes a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (c) has an additional segment in the N-terminal region and a distinct and longer C-terminus, compared to isoform a.
      Source sequence(s)
      BX647906
      Consensus CDS
      CCDS41600.1
      UniProtKB/TrEMBL
      B4DPV7
      Related
      ENSP00000369897.4, ENST00000380525.9
      Conserved Domains (3) summary
      cd00672
      Location:113 → 528
      CysRS_core; catalytic core domain of cysteinyl tRNA synthetase
      cd10310
      Location:3 → 76
      GST_C_CysRS_N; Glutathione S-transferase C-terminal-like, alpha helical domain of Cysteinyl-tRNA synthetase from higher eukaryotes
      PTZ00399
      Location:91 → 822
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    2. NM_001194997.2 → NP_001181926.1  cysteine--tRNA ligase, cytoplasmic isoform e

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) includes an additional in-frame exon in the 5' coding region, compared to variant 1, resulting in an isoform (e) that is longer than isoform a.
      Source sequence(s)
      AC131971, AI432096, AK298514, DC376478
      UniProtKB/TrEMBL
      B4DPV7
      Conserved Domains (3) summary
      cd00672
      Location:113 → 528
      CysRS_core; catalytic core domain of cysteinyl tRNA synthetase
      cd10310
      Location:3 → 76
      GST_C_CysRS_N; Glutathione S-transferase C-terminal-like, alpha helical domain of Cysteinyl-tRNA synthetase from higher eukaryotes
      PTZ00399
      Location:91 → 787
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    3. NM_001378136.1 → NP_001365065.1  cysteine--tRNA ligase, cytoplasmic isoform f

      Status: REVIEWED

      Source sequence(s)
      AC108448, AC131971, AK296763
      Consensus CDS
      CCDS91411.1
      UniProtKB/TrEMBL
      B4DKY1, E9PPK8, Q53HG6
      Related
      ENSP00000432619.2, ENST00000529772.5
      Conserved Domains (1) summary
      PTZ00399
      Location:28 → 717
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    4. NM_001378137.1 → NP_001365066.1  cysteine--tRNA ligase, cytoplasmic isoform g

      Status: REVIEWED

      Source sequence(s)
      AC108448, AC131971
      UniProtKB/TrEMBL
      A8MVQ3, B4DI19
      Conserved Domains (1) summary
      PTZ00399
      Location:28 → 729
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    5. NM_001378138.1 → NP_001365067.1  cysteine--tRNA ligase, cytoplasmic isoform h

      Status: REVIEWED

      Source sequence(s)
      AC108448, AC131971
      UniProtKB/TrEMBL
      B4DI19
      Conserved Domains (1) summary
      PTZ00399
      Location:28 → 694
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    6. NM_001378139.1 → NP_001365068.1  cysteine--tRNA ligase, cytoplasmic isoform h

      Status: REVIEWED

      Source sequence(s)
      AC108448, AC131971
      UniProtKB/TrEMBL
      B4DI19
      Conserved Domains (1) summary
      PTZ00399
      Location:28 → 694
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    7. NM_001378140.1 → NP_001365069.1  cysteine--tRNA ligase, cytoplasmic isoform i

      Status: REVIEWED

      Source sequence(s)
      AC108448, AC131971
      UniProtKB/TrEMBL
      B4DI19
      Conserved Domains (1) summary
      PTZ00399
      Location:1 → 647
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    8. NM_001751.6 → NP_001742.1  cysteine--tRNA ligase, cytoplasmic isoform b

      See identical proteins and their annotated locations for NP_001742.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site that causes a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (b) has a longer and distinct C-terminus, compared to isoform a.
      Source sequence(s)
      BC002880
      Consensus CDS
      CCDS7742.1
      UniProtKB/Swiss-Prot
      P49589, Q53XI8, Q5HYE4, Q9HD24, Q9HD25
      UniProtKB/TrEMBL
      Q53HG6
      Related
      ENSP00000380300.5, ENST00000397111.9
      Conserved Domains (1) summary
      PTZ00399
      Location:3 → 739
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    9. NM_139273.4 → NP_644802.1  cysteine--tRNA ligase, cytoplasmic isoform a

      See identical proteins and their annotated locations for NP_644802.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) consists of 22 exons and encodes the shortest isoform (a).
      Source sequence(s)
      AF288207, AI608729, DC376478
      Consensus CDS
      CCDS41602.1
      UniProtKB/TrEMBL
      Q53HG6
      Related
      ENSP00000278224.9, ENST00000278224.13
      Conserved Domains (2) summary
      cd00672
      Location:30 → 445
      CysRS_core; catalytic core domain of cysteinyl tRNA synthetase
      PTZ00399
      Location:3 → 704
      PTZ00399; cysteinyl-tRNA-synthetase; Provisional

    RNA

    1. NR_036542.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) includes an additional exon in the 5' region, and uses an alternate splice site in both the 5' and 3' regions, compared to variant 1. This variant is represented as non-coding because the use of the supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC108448, AI432096, AK096313, DC376478
      Related
      ENST00000531387.5

    2. NR_165428.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC108448, AC131971

    3. NR_165429.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC108448, AC131971

    4. NR_165430.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC108448, AC131971

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      3000929..3057423 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047427673.1 → XP_047283629.1  cysteine--tRNA ligase, cytoplasmic isoform X2

      UniProtKB/TrEMBL
      A8K067

    2. XM_047427672.1 → XP_047283628.1  cysteine--tRNA ligase, cytoplasmic isoform X1

      UniProtKB/TrEMBL
      B4DPV7

    3. XM_047427674.1 → XP_047283630.1  cysteine--tRNA ligase, cytoplasmic isoform X3

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187585.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      231991..288455 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054328872.1 → XP_054184847.1  cysteine--tRNA ligase, cytoplasmic isoform X1

      UniProtKB/TrEMBL
      B4DPV7

    2. XM_054328873.1 → XP_054184848.1  cysteine--tRNA ligase, cytoplasmic isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      3090162..3146645 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054370125.1 → XP_054226100.1  cysteine--tRNA ligase, cytoplasmic isoform X2

      UniProtKB/TrEMBL
      A8K067

    2. XM_054370124.1 → XP_054226099.1  cysteine--tRNA ligase, cytoplasmic isoform X1

      UniProtKB/TrEMBL
      B4DPV7

    3. XM_054370126.1 → XP_054226101.1  cysteine--tRNA ligase, cytoplasmic isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001014438.1: Suppressed sequence

      Description
      NM_001014438.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P49589.3 GenPept UniProtKB/Swiss-Prot:P49589

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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